IP Library Granted Patent US 9,114,107
Granted Patent B2
US 9,114,107 · App. 13/876,876 · Granted Aug 25, 2015

Compositions for inhibiting virus entry and promoting virolysis, and methods thereof

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Quick Facts
Patent No.
US 9,114,107
App. No.
13/876,876
Granted
Aug 25, 2015
Kind
B2
Abstract

The present invention includes a composition comprising a gold nanoparticle complexed with a cysteine-containing compound. The invention also includes the method of preparing a composition comprising a gold nanoparticle complexed with a cysteine-containing compound. The invention further includes a method of causing virolysis of a virus using the compositions described therein. The invention further includes a method of inhibiting virus entry using the compositions described therein.

Claims (56)

1. A composition comprising a peptide of formula (II) or a salt thereof:

(I),

(SEQ ID NO: 2)

Arg Ile Asn Asn Ile X Trp Ser Glu Ala Met Met βA 

Gln βA Cys-NH 2 ,

wherein: X is (2,4)-4-(4-ferrocenyl-1H-1,2,3-triazol-1-yl)pyrrolidine-2-carboxylic acid, and βA is beta-alanine.

2. The composition of claim 1 , further comprising at least one gold nanoparticle, wherein the at least one nanoparticle is complexed to the peptide of formula (II) through the Cys thiol group of SEQ ID NO:2.

3. The composition of claim 1 , further comprising at least one additional compound for treating viral infections.

4. The composition of claim 1 , wherein the peptide is encapsulated in a hydrogel.

5. A method of preparing a derivatized gold nanoparticle, wherein the gold nanoparticle is complexed with a binding molecule or a salt thereof, the method comprising:

contacting a solution of the binding molecule with the nanoparticle to generate a reaction system;

stirring the reaction system for an amount of time, whereby the derivatized gold nanoparticle is formed; and

isolating the derivatized gold nanoparticle from the reaction system,

wherein the binding molecule comprises a peptide of formula (II) or a salt thereof:

(II),

(SEQ ID NO: 2)

Arg Ile Asn Asn Ile X Trp Ser Glu Ala Met Met βA

Gln βA Cys-NH 2 ,

wherein X is (2,4)-4-(4-ferrocenyl-1H-1,2,3-triazol-1-yl)pyrrolidine-2-carboxylic acid, and βA is beta-alanine;

wherein the nanoparticle is complexed to the peptide of formula (II) through the Cys thiol group of SEQ ID NO:2.

6. A method of promoting virolysis of a virus in a mammal, wherein the virus is selected from the group consisting of human immunodeficiency virus type 1 (HIV-1), influenza, ebola and dengue, the method comprising administering to the mammal a therapeutically effective amount of a composition comprising at least one pharmaceutically acceptable carrier and at least one gold nanoparticle, wherein the gold nanoparticle is complexed with a binding molecule or a salt thereof, wherein the binding molecule comprises:

a peptide of formula (II) or a salt thereof:

(II),

(SEQ ID NO: 2)

Arg Ile Asn Asn Ile X Trp Ser Glu Ala Met Met βA

Gln βA Cys-NH 2 ,

wherein X is (2,4)-4-(4-ferrocenyl-1H-1,2,3-triazol-1-yl)pyrrolidine-2-carboxylic acid, and βA is beta-alanine;

wherein the nanoparticle is complexed to the peptide of formula (II) through the Cys thiol group of SEQ ID NO:2;

whereby virolysis of the virus in the mammal is promoted.

7. The method of claim 6 , wherein the mammal is further administered at least one additional compound for treating viral infections.

8. The method of claim 6 , wherein the peptide is encapsulated in a hydrogel.

9. The method of claim 6 , wherein the mammal is human.

10. A method of reducing the rate of or inhibiting entry of a virus into a cell of a mammal, wherein the virus is selected from the group consisting of human immunodeficiency virus type 1 (HIV-1), influenza, ebola and dengue, the method comprising administering to the mammal a therapeutically effective amount of a composition comprising at least one pharmaceutically acceptable carrier and at least one gold nanoparticle, wherein the gold nanoparticle is complexed with a binding molecule or a salt thereof, wherein the binding molecule comprises

a peptide of formula (II) or a salt thereof:

(II),

(SEQ ID NO: 2)

Arg Ile Asn Asn Ile X Trp Ser Glu Ala Met Met βA

Gln βA Cys-NH 2 ,

wherein X is (2,4)-4-(4-ferrocenyl-1H-1,2,3-triazol-1-yl)pyrrolidine-2-carboxylic acid, and βA is beta-alanine;

wherein the nanoparticle is complexed to the peptide of formula (II) through the Cys thiol group of SEQ ID NO:2;

whereby the entry of the virus into the cell of the mammal is inhibited or takes place at a reduced rate as compared to an untreated mammal.

11. The method of claim 10 , wherein the mammal is further administered at least one additional compound useful for treating viral infections.

12. The method of claim 10 , wherein the peptide is encapsulated in a hydrogel.

13. The method of claim 10 , wherein the mammal is human.

14. A method of reducing or treating infection of a virus in a mammal, wherein the virus is selected from the group consisting of human immunodeficiency virus type 1 (HIV-1), influenza, ebola and dengue, the method comprising administering to the mammal a therapeutically effective amount of a composition comprising at least one pharmaceutically acceptable carrier and at least one gold nanoparticle, wherein the gold nanoparticle is complexed with a binding molecule or a salt thereof, wherein the binding molecule comprises

a peptide of formula (II) or a salt thereof:

(II),

(SEQ ID NO: 2)

Arg Ile Asn Asn Ile X Trp Ser Glu Ala Met Met βA

Gln βA Cys-NH 2 ,

wherein X is (2,4)-4-(4-ferrocenyl-1H-1,2,3-triazol-1-yl)pyrrolidine-2-carboxylic acid, and βA is beta-alanine;

wherein the nanoparticle is complexed to the peptide of formula (II) through the Cys thiol group of SEQ ID NO:2;

whereby the infection of the virus in the mammal is reduced or treated.

15. The method of claim 14 , wherein the mammal is further administered at least one additional compound for treating viral infections.

16. The method of claim 14 , wherein the peptide is encapsulated in a hydrogel.

17. The method of claim 14 , wherein the mammal is human.

Assignments (3)
MERGER Recorded Jan 14, 2015
From: PHILADELPHIA HEALTH & EDUCATION CORPORATION
To: DREXEL UNIVERSITY
Reel/Frame 034764/0236 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 1, 2013
From: CHAIKEN, IRWIN; BASTIAN, ARANGASSERY ROSEMARY; -, KANTHARAJU
To: PHILADELPHIA HEALTH AND EDUCATION CORPORATION D/B/A DREXEL UNIVERSITY COLLEGE OF MEDICINE
Reel/Frame 031529/0347 →
CONFIRMATORY LICENSE Recorded Sep 27, 2013
From: DREXEL UNIVERSITY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 031302/0044 →